Cephalexin: Microbiological effects and pharmacologic parameters in man

Abstract

Cephalexin (desacetoxycephaloglycin), a semisynthetic derivative of cephalosporin C, was found to have a range of antimicrobial activity similar to that of cephalothin which inhibits the in vitro growth of most gram‐positive bacteria, with the exception of the enterococci and of some gram‐negative organisms. Except for methicillin‐resistant strains, all 62 strains of Staphylococcus aureus, including penicillin‐resistant strains, were inhibited by from 0.15 to 12.5 µg per milliliter of the drug. Eleven strains of methicillin‐resistant Staph. aureus were highly resistant to cephalexin; most were inhibited by 100 µg per milliliter. Among the other susceptible species were Streptococcus pyogenes, Streptococcus viridans, Diplococcus pneumoniae, most strains of Salmonella, Shigella, and Hemophilus influenzae, approximately 50 per cent of Escherichia coli, and almost one third of Proteus isolates. Enterococci, Aerobacter aerogenes, Pseudomonas aeruginosa, Alcaligenes fecalis, and Serratia were highly resistant. In man, following ingestion of 500 mg. in the fasting state, peak levels of 18 µg per milliliter were attained in the serum at one hour, whereas after a meal the level was 12 µg per milliliter. From 75 to 100 per cent of the oral dose was excreted in the urine within the first 8 hours, producing urinary levels in some specimens of over 1,000 µg of cephalexin per milliliter of urine. The minimum inhibitory concentration of cephalexin for sensitive organisms fell within the range of serum concentrations produced by ingestion of 500 mg. of this drug.